title: Efficacy, long-term safety, and tolerability of ziprasidone in children and adolescents with bipolar disorder.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the short- and long-term efficacy and safety of ziprasidone in children and adolescents with bipolar I disorder.
  
  
  METHODS
  Subjects 10-17 years of age with a manic or mixed episode associated with bipolar I disorder participated in a 4 week, randomized, double-blind, placebo-controlled multicenter trial (RCT) followed by a 26 week open-label extension study (OLE). Subjects were randomized 2:1 to initially receive flexible-dose ziprasidone (40-160 mg/day, based on weight) or placebo. Primary outcome was the change in Young Mania Rating Scale (YMRS) scores from baseline. Safety assessments included weight and body mass index (BMI), adverse events (AEs), vital signs, laboratory measures, electrocardiograms, and movement disorder ratings.
  
  
  RESULTS
  In the RCT, 237 subjects were treated with ziprasidone (n=149; mean age, 13.6 years) or placebo (n=88; mean age, 13.7 years). The estimated least squares mean changes in YMRS total (intent-to-treat population) were -13.83 (ziprasidone) and -8.61 (placebo; p=0.0005) at RCT endpoint. The most common AEs in the ziprasidone group were sedation (32.9%), somnolence (24.8%), headache (22.1%), fatigue (15.4%), and nausea (14.1%). In the OLE, 162 subjects were enrolled, and the median duration of treatment was 98 days. The mean change in YMRS score from the end of the RCT to the end of the OLE (last observation carried forward) was -3.3 (95% confidence interval, -5.0 to -1.6). The most common AEs were sedation (26.5%), somnolence (23.5%), headache (22.2%), and insomnia (13.6%). For both the RCT and the OLE, no clinically significant mean changes in movement disorder scales, BMI z-scores, liver enzymes, or fasting lipids and glucose were observed. One subject on ziprasidone in the RCT and none during the OLE had Fridericia-corrected QT interval (QTcF) ≥ 460 ms.
  
  
  CONCLUSIONS
  These results demonstrate that ziprasidone is efficacious for treating children and adolescents with bipolar disorder. Ziprasidone was generally well tolerated with a neutral metabolic profile.
  
  
  BACKGROUND
  NCT00257166 and NCT00265330 at ClinicalTrials.gov.
authors.affiliation: 1 Department of Child and Adolescent Psychiatry, Johns Hopkins University and the Kennedy Krieger Institute , Baltimore, Maryland.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.forename: Idil
authors.initials: I
authors.lastname: Cavuş
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pappadopulos
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Vanderburg
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Schwartz
authors.forename: Balarama K
authors.initials: BK
authors.lastname: Gundapaneni
authors.forename: Melissa P
authors.initials: MP
authors.lastname: DelBello
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010879:Piperazines / Q000009:adverse effects* / Q000627:therapeutic use*; D013844:Thiazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone